Chiral catalysts and processes for preparing the same

ABSTRACT

A novel catalyst comprising the formula: ##STR1## and which has utility in areas such as epoxidation of olefins.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to the field of asymmetric catalysis. Moreparticularly, the invention relates to the field of organometalliccatalysts useful for enantioselectively epoxidizing prochiral olefinsand a new class of amid-salicylidene ligands and their metal complexes(i.e. an optically active metal ligand complex catalyst) as novelligands and novel catalysts.

Asymmetric epoxidation of olefins constitutes an extremely appealingstrategy for the synthesis of optically active organic compounds.Several advances in this area have occurred in recent years. The mostcommonly and successfully used catalysts for asymmetric epoxidation ofunfunctionalized olefins are porphyrin and salen based systems. Chiralmetal porphyrins have been reported to catalyze asymmetric epoxidationof styrene derivatives with high turnover numbers and moderateenantioselectivities (J. P. Collman et al. Science, 1993, 26, 1404).Unfortunately, the chiral porphyrin systems are usually difficult toprepare and are limited to styrene derivatives as substrates. E. N.Jacobsen (J. Am. Chem. Soc. 1990, 112, 2801 ) and T. Katssuki(Tetrahedron Lett. 1990, 31, 7345) independently reported asymmetricepoxidation of olefins by bleach or iodosobenzene catalyzed by chiralmanganese salen complexes. These chiral salen complexes were designedbased on Kochi's achiral cationic mangangese salen complex that wasreported in 1986 (J. Am. Chem. Soc. 1986, 108, 108, 2309). The salenbased catalysts gave very high enantioselectivities for the epoxidationof cis olefins, e.g. cis-beta-methylstyrene and dihydronaphthalene.However, the turnover numbers of these catalysts are typically 10-30,and they are limited to conjugated cis olefins.

Given the broad synthetic utility of chiral epoxides, more efficientcatalytic and enantioselective catalysts besides porphyrin and salensystems for asymmetric epoxidation of unfunctionalized olefins areclearly desirable.

2. Description of the Prior Art

The following prior art references are disclosed in accordance with theterms of 37 CFR 1.56, 1.97, and 1.93.

U.S. Pat. No. 4,471,130 discloses methods for asymmetric epoxidation ofallylic alcohols.

U.S. Pat. No. 4,594,439 discloses methods for asymmetric epoxidation ofcarbinals using a titanium catalyst.

U.S. Pat. No. 4,924,011 discloses a process for preparing taxol.

U.S. Pat. No. 5,352,814 discloses methods for asymmetric epoxidation ofolefins using an optically active manganese complex.

PCT WO 93/03838 (published Mar. 4, 1993) discloses chiral catalystsuseful for epoxidizing prochiral olefins.

PCT WO 93/12260 (published Jun. 24, 1993) discloses a class ofasymmetric ligands preferably derived from 2-diphenylphosphinobenzoicacid as an ester or amide from chiral alcohols and chiral amines.

Journal of American Chemical Society, Vol. 110, pages 4087-4089, issued1988 (ACS), Yoon et al., discloses "Catalysis of Alkene Oxidation byNickel Salen Complexes Using NaOCl under Phase-Transfer Conditions".

Coordination Chemistry Reviews 140, (1995) pp. 189-214, T. Katsuki;Elsevier Science S.A. discloses salen-manganese complexes as catalystsfor asymmetric oxidations of unfunctionalized olefins.

Catalytic Asymmetric Synthesis, Iwao Ojima--Editor (1993), VCHPublishers, Inc., pp. 159-202; "Asymmetric Catalytic Epoxidation ofUnfunctionalized Olefins" by Eric N. Jacobsen discloses salen-manganesecomplexes as catalysts for asymmetric oxidations of unfunctionalizedolefins.

Journal of American Chemical Society, Vol. 112, No. 7, pages 2801-2803,issued Mar. 28, 1990 (ACS), Zhang et al., discloses "EnantioselectiveEpoxidation of Unfunctionalized Olefins Catalyzed by (Salen) ManganeseComplexes".

Journal of American Chemical Society, Vol. 113, No. 18, pages 7062-4,issued Aug. 28, 1991 (ACS), Jacobsen et al., discloses "HighlyEnantioselective Epoxidation Catalysts Derived from1,2-Diaminocyclohexane".

Bulletin Chemical Society of Japan, Vol. 56, No. 1, issued January,1983, Kanatomi, discloses "The Dehydrogenation of Nickel (II) Chelatesof rac- and meso-2,2'-[(1,2-Diphenylethylene)bis(iminomethylene)diphenol and RelatedCompounds".

Chemistry Letters, issued 1986, pages 1483-6 (The Chemical Society ofJapan), Nakajima et al., discloses "Asymmetric Oxidation of Sulfides toSulfoxides by Organic Hydroperoxides with Optically Active SchiffBase--Oxovanadium (IV) Catalysts".

Journal of American Chemical Society, Vol. 113, No. 17, pages 6703-4,issued August 14, 1991 (ACS), Jacobsen et al., discloses "ElectronicTuning of Asymmetric Catalysts".

All of the above-cited prior art and any other references mentionedherein are incorporated herein by reference in their entirety.

SUMMARY OF THE INVENTION

The present invention provides a novel catalyst having the formula:##STR2## wherein M, A, R, (C₁), (C_(n)), and (C₂) are defined herein.Such catalyst has unique utility in areas such as epoxidation ofolefins, particularly unfunctionalized olefins.

DETAILED DESCRIPTION OF THE INVENTION

In one facet of the present invention, there is provided new and novelligands having the general formula: ##STR3##

In this formula II, R₁ and R₂ are independently selected from the groupconsisting of hydrogen; alkyl C₁ -C₅₀ ; substituted and unsubstitutedphenyl, naphthyl, and anthracyl; and a cyclic ring encompassing both R₁and R₂ and containing a total of 3 to 50 atoms selected from the groupconsisting of carbon atoms, oxygen atoms, nitrogen atoms, sulfur atoms;and mixtures thereof, with the proviso that the substituents on thealkyl, phenyl, naphthyl, anthracyl, and cyclic rings can be nitro,halogen, alkoxy, carboxylate, amino, amide, silyl, and siloxyl; R₃ isselected from the group consisting of hydrogen and alkyl C₁ -C₂₀. R₃ andR₄ are independently selected from the group consisting of substitutedand unsubstituted alkyl and aryl; nitro; halogen; hydrogen; alkoxy;carboxylate; amino; amide; silyl; and siloxyl. R₄ and R₅, R₅ and R₆, andR and R₇ may also (in addition to the above) form a cyclic ringcontaining a total of 2 to 6 atoms selected from the group consisting ofcarbon atoms, oxygen atoms, nitrogen atoms, sulfur atoms, and mixturesthereof and said ting can be substituted or unsubstituted.

R₁₀ and R₁₁ are independently selected from the group consisting ofhydrogen, alkyl C₁ -C₂₀, substituted and unsubstituted phenyl, naphthyl,and anthracyl, and a cyclic ting encompassing both R₁₀ and R₁₁ andcontaining a total of 2 to 6 atoms selected from the group consisting ofcarbon atoms, oxygen atoms, nitrogen atoms, sulfur atoms, and mixturesthereof. n is either 0, 1, or 2; and (C₁), C_(n)), and (C₂) areindependently or jointly part of an unsubstituted or substituted arylgroup.

In another facet of the present invention, there is provided new andnovel catalysts having the general formula: ##STR4## wherein in formulaI above, R₁ -R₁₁ have the same meaning as set forth in formula II.Additionally, in this formula I, the following definitions apply:

M is a transition metal ion and includes such metals as manganese,cobalt, nickel, chromium, iron, rhenium, ruthenium, rhodium, technetium,palladium, platinum, osmium, copper, tellurium, titanium, vanadium,molybdenum, and gadolinium; and A is an anion and includes halides(chlorine, fluorine, bromine, and iodine); carboxylates; PF₆ ; BF₄ ;B(R)₄ ; and R wherein R is either a substituted or unsubstituted alkylor aryl; acetates; sulfonates; triflates; and tosylates.

A is not present when the metal selected for M has an oxidation state oftwo or less. Thus, if the metal selected for M is, for example, nickel(II), then the catalyst structural formula would be as follows: ##STR5##

Furthermore, the entire complex of Formula I can have positive ornegative charges from e.g. +3 to -2. depending upon the metal selectedfor M. The complex of Formula I can be in its hydrated form orcoordinated with one or more axial ligands. These axial ligands includealcohols, ketones, and substituted or unsubstituted amines or pyridinesand their N-oxides.

As used herein, the term "substituted" is contemplated to include allpermissible substituents of organic compounds. In a broad aspect, thepermissible substituents include acyclic and cyclic, branched andunbranched, carbocyclic and heterocyclic, aromatic and non-aromaticsubstituents of organic compounds. Illustrative substituents include,for example, those described hereinabove. The permissible substituentscan be one or more and the same or different for appropriate organiccompounds. For purposes of this invention, the heteroatoms such asnitrogen may have hydrogen substituents and/or any permissiblesubstituents of organic compounds described herein which satisfy thevalencies of the heteroatoms. This invention is not intended to belimited in any manner by the permissible substituents of organiccompounds.

The novel catalysts falling within formula I above may or may not havechiral carbon centers at (C₁) and/or (C₂). In certain cases, it has beenfound advantageous to have at least one chiral carbon center at (C₁) and(C₂).

Examples of the combination of "R" groups such as R₁ and R₂, whereinthere is found a cyclic ring, include the following: ##STR6## where R isalkyl or aromatic, substituted, or unsubstituted; and * connotates achiral center.

Examples of catalysts that fall within formula I include the following:##STR7## wherein M is a transition metal ion; A is an anion; and R₁ -R₂₁are independently selected from the group consisting of substituted andunsubstituted alkyl and aryl groups; nitro; hydrogen; halogen; alkoxy;carboxylate; amino; amide; silyl; and siloxyl. ##STR8##

In general, the novel tetradentate ligands of the present invention areprepared by the reaction of an acid (such as a substituted orunsubstituted picolinic acid) with a chiral diamine in the presence ofdicyclohexylcarbodiimide (DCC) and a catalytic amount ofN,N-dimethyl-4-amino pyridine (DMAP) in CH₂ Cl₂ to form a monoamide,followed by condensation with a substituted or unsubstitutedsalicylaldehyde to form the ligand. Scheme 1 shows an example of thepreparation of a tetradentrate ligand. ##STR9##

The novel catalysts of the present invention are prepared by reactingthe ligand with, for example, Mn(OAc)₃ and LiCl in an organicliquid/solvent such as ethanol. The catalyst in this example has thestructure as shown above in formula IV.

This facet of the present invention relates to asymmetric syntheses inwhich a prochiral or chiral compound is reacted in the presence ofoptically active, metal-ligand complex catalyst, in enantiomericallyactive form, to produce an optically active product.

Specifically, it has been unexpectedly found that the general catalyst,disclosed in the earlier part of this specification, can effectasymmetric synthesis in various processes with various substrates toproduce a material which is optically active.

The asymmetric syntheses processes of this invention are useful for theproduction of numerous optically active organic compounds, e.g.,epoxides, sulfoxides, aziridines, cyclopropanes, aldehydes, alcohols,ethers, esters, amines, amides, carboxylic acids and the like, whichhave a wide variety of applications.

This part of the subject invention encompasses the carrying out of anyknown conventional syntheses in an asymmetric fashion with the noveloptically active metal-ligand complex catalyst as disclosed herein. Asindicated above, the processes of this invention stereoselectivelyproduce an enantiomer. Preferred asymmetric syntheses reactions involvethe reaction of organic compounds with an oxygen atom source in thepresence of a catalytic amount of an optically active metal-ligandcomplex catalyst.

More preferably, the subject invention relates to asymmetric epoxidationwhich involves the use of an optically active metal-ligand complexcatalyst in the production of optically active epoxides wherein aprochiral or chiral olefinic compound is reacted with an oxygen atomsource. The processing techniques of this invention may correspond toany of the known processing techniques heretofore employed inconventional asymmetric synthesis reactions including asymmetricepoxidation reactions.

For instance, the asymmetric synthesis processes can be conducted incontinuous, semi-continuous, or batch fashion and involve a liquidrecycle and/or gas recycle operation as desired. Likewise, the manner ororder of addition of the reaction ingredients, catalyst, and solvent arealso not critical and may be accomplished in any conventional fashion.

In general, the asymmetric syntheses reactions are carded out in aliquid reaction medium that contains a solvent for the optically activecatalyst, preferably one in which the reaction ingredients, includingcatalyst, are substantially soluble.

As indicated above, the subject invention encompasses the carrying outof any known conventional syntheses in an asymmetric fashion in whichthe catalyst thereof is replaced by an optically active metal-ligandcomplex as disclosed herein.

Asymmetric oxidation of sulfides to sulfoxides can be carried out inaccordance with conventional procedures known in the art. For example,sulfides can be converted to optically active sulfoxides under oxidationconditions in the presence of an optically active metal-ligand complexcatalyst described herein.

Asymmetric oxidation of aldehydes to acids can be carried out inaccordance with conventional procedures known in the art. For example,optically active acids can be prepared by reacting a racemic aldehydeand an oxygen atom source in the presence of an optically activemetal-ligand complex catalyst described herein.

Asymmetric hydrocyanation can be carried out in accordance withconventional procedures known in the art. For example, optically activenitrile compounds can be prepared by reacting a prochiral olefinic andhydrogen cyanide under hydrocyanation conditions in the presence of anoptically active metal-ligand complex catalyst described herein.

Asymmetric olefin hydrosilylation can be carried out in accordance withconventional procedures known in the art. For example, optically activesilyl compounds can be prepared by reacting a prochiral olefin and asilyl compound under hydrosilylation conditions in the presence of anoptically active metal-ligand complex catalyst described herein.

Asymmetric ketone hydrosilylation can be carded out in accordance withconventional procedures known in the art. For example, optically activesilyl ethers or alcohols can be prepared by reacting a prochiral ketoneand a silyl compound under hydrosilylation conditions in the presence ofan optically active metal-ligand complex catalyst described herein.

Asymmetric aziridination can be carried out in accordance withconventional procedures known in the art. For example, prochiral olefinscan be converted to optically active aziridines under aziridanationconditions in the presence of an optically active metal-ligand complexcatalyst described herein.

Asymmetric hydroamidation can be carried out in accordance withconventional procedures known in the art. For example, optically activeamides can be prepared by reacting a prochiral olefin, carbon monoxide,and a primary or secondary amine or ammonia under hydroamidationconditions in the presence of an optically active metal-ligand complexcatalyst described herein.

Asymmetric olefin hydrogenations and other asymmetric hydrogenations canbe carried out in accordance with conventional procedures known in theart. For example, hydrogenation can be used to reduce a carbon-carbondouble bond to a single bond. Other double bonds can also behydrogenated, for example, a ketone can be converted to an opticallyactive alcohol under hydrogenation conditions in the presence of anoptically active metal-ligand complex catalyst described herein.

Asymmetric aminolysis can be carried out in accordance with conventionalprocedures known in the art. For example, optically active amines can beprepared by reacting a prochiral olefin with a primary or secondaryamine under aminolysis conditions in the presence of an optically activemetal-ligand complex catalyst described herein.

Asymmetric isomerization can be carried out in accordance withconventional procedures known in the art. For example, allylic alcoholscan be isomerized under isomerization conditions to produce opticallyactive aldehydes in the presence of an optically active metal-ligandcomplex catalyst described herein.

Asymmetric Grignard cross coupling can be carried out in accordance withconventional procedures known in the art. For example, optically activeproducts can be prepared by reacting a chiral Grignard reagent with analkyl or aryl halide under Grignard reagent with an alkyl or aryl halideunder Grignard cross coupling conditions in the presence of an opticallyactive metal-ligand complex catalyst described herein.

Asymmetric transfer hydrogenation can be carded out in accordance withconventional procedures known in the art. For example, optically activealcohols can be prepared by reacting a prochiral ketone and an alcoholunder transfer hydrogenation conditions in the presence of an opticallyactive metal-ligand complex catalyst described herein.

Asymmetric olefin hydroboration can be carried out in accordance withconventional procedures known in the art. For example, optically activealkyl boranes or alcohols can be prepared by reacting a prochiral olefinand a borane under hydroboration conditions in the presence of anoptically active metal-ligand complex catalyst described herein.

Asymmetric olefin cyclopropanation can be carried out in accordance withconventional procedures known in the art. For example, optically activecyclopropanes can be prepared by reacting a prochiral olefin and a diazocompound under cyclopropanation conditions in the presence of anoptically active metal-ligand complex catalyst described herein.

Asymmetric aldol condensations can be carried out in accordance withconventional procedures known in the art. For example, optically activealdols can be prepared by reacting a prochiral ketone or aldehyde and asilyl enol ether under aldol condensation conditions in the presence ofan optically active metal-ligand complex catalyst described herein.

Asymmetric olefin codimerization can be carded out in accordance withconventional procedures known in the art. For example, optically activehydrocarbons can be prepared by reacting a prochiral alkene and analkene under codimerization conditions in the presence of an opticallyactive metal-ligand complex catalyst described herein.

Asymmetric allylic alkylation can be carried out in accordance withconventional procedures known in the art. For example, optically activehydrocarbons can be prepared by reacting a prochiral ketone or aldehydeand an allylic alkylating agent under alkylation conditions in thepresence of an optically active metal-ligand complex catalyst describedherein.

Asymmetric Diels-Alder reaction can be carried out in accordance withconventional procedures known in the art. For example, optically activeolefins can be prepared by reacting a prochiral diene and an olefinunder cycloaddition conditions in the presence of an optically activemetal-ligand complex catalyst described herein.

The permissible prochiral and chiral starting material reactantsencompassed by the processes of this invention are, of course, chosendepending on the particular asymmetric synthesis desired. Such startingmaterials are well known in the art and can be used in conventionalamounts in accordance with conventional methods. Illustrative startingmaterial reactants include, for example, substituted and unsubstitutedaldehydes (intramolecular hydroacylation, aldol condensation, oxidationto acids, prochiral olefins (epoxidation, hydrocyanation,hydrosilylation, aziridination, hydroamidation, aminolysis,cyclopropanation, hydroboration, Diels-Alder reaction, codimerization),ketones (hydrogenation, hydrosilylation, aldol condensation, transferhydrogenation, allylic alkylation), epoxides (hydrocyanation,nucleophilic ring opening reaction), alcohols (carbonylation) acyl andaryl chlorides (decarbonylation), a chiral Grignard reagent (Grignardcross coupling) and the like.

The novel catalysts of the present invention thus have utility in a widevariety of chemical processes, and particularly, in asymmetric synthesisreaction which include, without limitation, epoxidation; hydroxylation;cyclopropanation; aziridination; Diels-Alder reactions; cycloaddition,Michael addition; Aldol reaction; hydroboration; olefin and ketonehydrosilylation; hydrocyanation; addition of Grignards ororganometallics to aldehydes and ketones; allylic alkylation; Grignardcross coupling; kinetic resolution; oxidation of aldehydes,hydroamidation; olefin isomerization; aminolysis; hydrogenation;hydrocarboxylation; oxidation of sulfides; oxidation of phosphines; andoxidation of selenides.

While the present invention catalysts have the above illustrated uses,the general discussion herein will focus around the epoxidation ofolefins, particularly unfunctionalized olefins.

Illustrative olefin starting material reactants useful in certain of theasymmetric synthesis processes of this invention, e.g. epoxidation,include those which can be terminally or internally unsaturated and beof straight chain, branched chain, or cyclic structure. Such olefins cancontain from 3 to 40 carbon atoms or greater and may contain one or moreethylenic unsaturated groups. Moreover, such olefins may contain groupsor substituents which do not essentially adversely interfere with theasymmetric synetheses process such as carbonyl, carbonyloxy, oxy,hydroxy, oxycarbonyl, halogen, alkoxy, aryl, haloalkyl, and the like.Illustrative olefinic unsaturated compounds include substituted andunsubstituted alpha olefins, internal olefins, alkyl alkenoates, alkenylalkanoates, alkenyl alkyl ethers, alkenols, and the like, e.g. 1-butene,1-pentene, 1-hexene, 1-octene, 1-decene, 1-dodecene, 1-octadecene,2-butene, isoamylene, 2-pentene, 2-hexene, 3-hexene, 2-heptene,cyclohexene, propylene dimers, propylene trimers, propylene tetramers,2-ethylhexene, 3-phenyl-1-propene, 1,4-hexadiene, 1,7-octadiene,3-cyclohexyl-1-butene, allyl alcohol, hex-1-en-4-ol, oct-1-en-4-ol,vinyl acetate, allyl acetate, aryloates such as vinyl benzoate and thelike, 3-butenyl acetate, vinyl propionate, allyl propionate, allylbutyrate, methyl methacrylate, 3-butenyl acetate, vinyl ethyl ether,vinyl methyl ether, allyl ethyl ether, n-propyl-7-octenoate, substitutedand unsubstituted chromenes, 3-butenenitrile, 5-hexenamide, styrene,indene, 1,2-dihydronaphthalene, norbornene, alpha-methylstyrene, and thelike. Illustrative preferred olefinic unsaturated compounds include, forexample, p-isobutylstyrene, 2-vinyl-6-methoxynaphthylene,3-ethenylphenyl phenyl ketone, 4-ethylphenyl-2-thienylketone,4-ethenyl-2-fluorobiphenyl,4-(1m,3-dihydro-1-oxo-2H-isoindol-2-yl)styrene,2-ethyl-5-benzoylthiophene, 3-ethenylphenyl phenyl ether,propenylbenzene, isobutyl-4-propenyl-benzene, phenyl vinyl ether, vinylchloride, and the like. Suitable olefinic unsaturated compounds usefulin certain asymmetric syntheses processes of this invention includesubstituted aryl ethylenes described in U.S. Pat. No. 4,329,507,incorporated herein by reference in its entirety. Of course, it isunderstood that mixtures of different olefinic starting materials can beemployed, if desired, by the asymmetric syntheses processes of thesubject invention. More preferably, the subject invention is especiallyuseful for the production of optically active materials, by epoxidationof alpha olefins containing from 3 to 40 carbon atoms or greater, aswell as starting material mixtures of such alpha olefins and internalolefins.

Illustrative prochiral and chiral olefins useful in the processes ofthis invention include those represented by the formula: ##STR10##wherein R₁, R₂, R₃, and R₄ are the same or different (provided R₁ isdifferent from R₂ and R₃ is different from R₄) and are selected fromhydrogen; alkyl; substituted alkyl, said substitution being selectedfrom amino including alkyamino and dialkylamino, such as benzylamino anddibenzylamino, hydroxy, alkoxy, such as methoxy and ethoxy, acyloxy,such as acetoxy, halo, nitro, nitrile, thio, carbonyl, carboxamide,carboxaldehyde, carboxyl, carboxylic ester; aryl including phenyl;substituted aryl including phenyl, said substitution being selected fromalkyl, amino including alkylamino and dialkylamino such as benzylaminoand dibenzylamino; hydroxy, alkoxy such as methoxy and ethoxy, acyloxysuch as acetoxy, halo, nitrile, nitro, carboxyl, carboxaldehyde,carboxylic ester, carbonyl, and thio, said aryl substitution being lessthan four substituents; acyloxy such as acetoxy; alkoxy such as methoxyand ethoxy; amino including alkylamino and dialkylamino such asbenzylamino and dibenzylamino; acylamino and diacylamino such asacetylbenzylamino and diacetylamino; nitro; carbonyl; nitrile; carboxyl;carboxamide; carboxaldehyde; carboxylic ester; and alkylmercapto such asmethylmercapto.

It is understood that the prochiral and chiral olefins of thisdefinition also include molecules of the above general formula where theR-groups are connected to form ring compounds, e.g.,2-methyl-1-cyclohexene, and the like.

In accordance with the epoxidation process of the present invention, theprochiral olefin, an oxygen atom source, and the chiral catalyst arereacted under such conditions and for such time as is needed toepoxidize said olefin. In addition to those olefins set forth above, theprochiral olefin can be selected from mono-substituted,1,1-disubstituted, cis-1,2-disubstituted, trans-1,2-disubstituted,trisubstituted, and tetrasubstituted. Of these, the monosubstituted andcis-1,2-disubstituted have shown the highest ee values.

Preferably, the prochiral olefin to be epoxidized is selected from thegroup consisting of cis-disubstituted olefins, including cyclic olefins,bearing a sterically demanding substituent on one end and a smallersubstituent on the other end. More preferably, the prochiral olefin is acis disubstituted olefin with a primary substituent on one side of thedouble bond and a second, tertiary, or aryl substituent on the otherside.

The prochiral olefin can also be selected from the group consisting ofenamines, enols, and alpha, beta-unsaturated carbonyls. More preferably,the prochiral olefin is selected from the group consisting ofcis-β-methyl-styrene, dihydronaphthalene, 2-cyclohexenyl-1,1-dioxolane,propylene, styrene, and 2,2-dimethylcyclochromene. Most preferably, theprochiral olefin is cis-β-methylstyrene.

The oxygen atom source used in the epoxidation reaction should be anoxidant which is relatively unreactive toward olefins under mildconditions. Preferably, the oxygen atom source is selected from thegroup consisting of NaOCl, iodosylmesitylene, NaIO₄, NBu₄ IO₄, potassiumperoxymonosulfate, magnesium monoperoxyphthalate, and hexacyanoferrateion. More preferably, the oxygen atom source is selected from the groupconsisting of NaOCl and iodosomesitylene. For economic reasons, the mostpreferred oxygen atom source is NaOCl. Thus, a preferred method usesNaOCl as the oxygen atom source.

The amount of optically active complex catalyst in the reaction mediumof a given process of this invention need only be that minimum amountnecessary to catalyze the particular asymmetric syntheses processdesired. In general, concentrations in the range of from about 1 ppm toabout 10,000 ppm, based on the starting reactant, should be sufficientfor most asymmetric syntheses processes. For example, in the catalyzedasymmetric epoxidation processes of this invention, it is generallypreferred to employ from about 10 to 1000 ppm and more preferably from25 to 750 ppm.

The process conditions employable in the asymmetric processes of thisinvention are, of course, chosen depending on the particular asymmetricsyntheses desired. Such process conditions are well known in the art.All of the asymmetric syntheses processes of this invention can becarried out in accordance with the conventional procedures known in theart. Illustrative reaction conditions for conducting the asymmetricsyntheses processes of this invention are described, for example, inBosnich, B., Asymmetric Catalysis, Martinus Nijhoff Publishers. 1986 andMorrison, James D., Asymmetric Synthesis, Vol. 5, Chiral Catalysis,Academic Press. Inc., 1985, both of which are incorporated herein byreference in their entirety. Depending on the particular process,operating temperatures can range from about -80° C. or less to about500° C. or greater and operating pressures can range from about 1 psiaor less to about 10,000 psia or greater.

The reaction conditions of effecting, for example, the asymmetricepoxidation process of this invention may be those heretoforeconventionally used and may comprise a reaction temperature of fromabout -25° C. or lower to about 200° C. or higher and pressures rangingfrom about 1 to about 10,000 psia. While one example of the asymmetricsyntheses process is the epoxidation of olefinically unsaturatedcompounds and more preferably olefinic hydrocarbon, to produce opticallyactive epoxides, it is to be understood that the optically activemetal-ligand complexes may be employed as catalysts in other types ofasymmetric syntheses processes to obtain good results. Moreover, whilesuch other asymmetric syntheses may be performed under their usualconditions, in general, it is believed that they may be performed atlower temperatures than normally preferred due to the optically activemetal-ligand complex catalysts.

The total gas pressure of the oxygen atom source and, for example,olefinic unsaturated starting compound of one asymmetric (epoxidation)process of this invention may range from about 1 to about 10,000 psia.More preferably, however, in the asymmetric epoxidation of prochiralolefins to produce optically active epoxides, it is preferred that theprocess be operated at a total gas pressure of less than about 150 psia,and more preferably less than about 1000 psia. The minimum totalpressure of the reactants is not particularly critical and is limitedpredominately only by the amount of reactants necessary to obtain adesired rate of reaction.

In general, the processes of this invention may be conducted at areaction temperature from about -25° C. or lower to about 200° C. Thepreferred reaction temperature employed in a given process will, ofcourse, be dependent upon the particular starting material and opticallyactive metal-ligand complex catalyst employed as well as the efficiencydesired. Lower reaction temperatures may generally tend to favor higheree. For example, asymmetric epoxidations at reaction temperatures ofabout -20° C. to about 120° C. are preferred for all types of olefinicstarting materials. More preferably, alpha-olefins can be effectivelyepoxidated at a temperature of from about 0° C. to about 90° C. whileeven less reactive olefins than conventional linear alpha-olefins andinternal olefins, as well as mixtures of alpha-olefins and internalolefins, are effectively and preferably epoxidated at a temperature offrom about 0° C. to about 50° C.

The processes are conducted for a period of time sufficient to producethe optically active products. The exact time employed is dependent, inpart, upon factors such as temperature, nature, and proportion ofstarting materials, and the like. The reaction time will normally bewithin the range of from about one-half to about 200 hours or more, andpreferably from less than about 1 to 10 hours.

The asymmetric syntheses process (for example, asymmetric epoxidationprocess) of this invention can be carried out in either the liquid orgaseous state and involve a batch, continuous liquid or gas recyclesystem, or combination of such systems. A batch system is preferred forconducting the processes of this invention. Preferably, asymmetricepoxidation of this invention involves a batch homogeneous catalysisprocess wherein the epoxidation is carried out in the presence of anysuitable conventional solvent as further outlined herein.

The asymmetric syntheses processes of this invention may be conducted inthe presence of an organic solvent for the optically active metal-ligandcomplex catalyst. Depending on the particular catalyst and reactantsemployed, suitable organic solvents include, for example, alcohols,alkanes, alkenes, alkenes, ethers, aldehydes, ketones, esters, acids,amides, amines, aromatics, and the like. Any suitable solvent which doesnot unduly adversely interfere with the intended asymmetric synthesesprocess can be employed and such solvents may include those heretoforecommonly employed in known metal catalyzed processes. Increasing thedielectric constant or polarity of a solvent may generally tend to favorincreased reaction rates.

Mixtures of one or more different solvents may be employed if desired.It is obvious that the amount of solvent is not critical to the subjectinvention and need only be that amount sufficient to provide thereaction medium with the particular metal concentration desired for agiven process. In general, the amount of solvent when employed may rangefrom about 5% by weight up to about 95% by weight or more, based on thetotal weight of the reaction medium.

The processes of this invention are useful for preparing substituted andunsubstituted optically active compounds. The processes of thisinvention stereo-selectively produce a chiral center. Illustrativeoptically active compounds prepared by the processes of this inventioninclude, for example, substituted and unsubstituted alcohols or phenols;amines; amides; ethers or epoxides; esters; carboxylic acids oranhydrides; ketones; olefins; acetylenes; halides or sulfonates;aldehydes; nitriles; and hydrocarbons. Illustrative of suitableoptically active compounds which can be prepared by the processes ofthis invention (including derivatives of the optically active compoundsdescribed hereinbelow and also prochiral and chiral starting materialcompounds as described hereinabove) include those permissible compoundswhich are described in Kirk-Othmer, Encyclopedia of Chemical Technology,Third Edition, 1984, the pertinent portions of which are incorporatedherein by reference in their entirety, and The Merck Index, AnEncyclopedia of Chemicals, Drugs, and Biologicals, Eleventh Edition,1989, the pertinent portions of which are incorporated herein byreference in their entirety.

The processes of this invention can provide optically active productshaving very high enantioselectivity and regioselectivity, e.g.,epoxidation. Enantiomeric excesses of preferably greater than 50% can beobtained by the processes of this invention. The processes of thisinvention can also be carried out at highly desirable reaction ratessuitable for commercial use.

The desired optically active products, e.g., epoxidates, may berecovered in any conventional manner. Suitable separation techniquesinclude, for example, solvent extraction, crystallization, distillation,vaporization, wiped film evaporation, falling film evaporation, and thelike. It may be desired to remove the optically active products from thereaction systems as they are formed through the use of trapping agentsas described in WO patent 88/08835.

The optically active products produced by the asymmetric synthesesprocesses of this invention can undergo further reaction(s) to afforddesired derivatives thereof. Such permissible derivatization reactionscan be carried out in accordance with conventional procedures known inthe art. Illustrative derivatization reactions include, for example,esterification oxidation of alcohols to aldehydes, N-alkylation ofamides, addition of aldehydes to amides, nitrile reduction, acylation ofketones by esters, acylation of amines, and the like.

Illustrative of suitable reactants in effecting the asymmetric synthesisprocesses of this invention include by way of example:

AL alcohols

PH phenols

THP thiophenols

MER mercaptans

AMN amines

AMD amides

ET ethers

EP epoxides

ES esters

H hydrogen

CO carbon monoxide

HCN hydrogen cyanide

HS hydrosilane

W water

GR grignard reagent

AH acyl halide

UR ureas

OS oxalates

CN carbamates

CNA carbamic acids

CM carbonates

CMA carbonic acids

CA carboxylic acids

ANH anhydrides

KET ketones

OLE olefins

ACE acetylenes

HAL halides

SUL sulfonates

ALD aldehydes

NIT nitriles

HC hydrocarbons

DZ diazo compounds

BOR boranes

ESE enol silyl ethers

SUD sulfides

Illustrative of suitable optically active products prepared by theasymmetric syntheses processes of this invention include by way ofexample:

AL alcohols

PH phenols

THP thiophenols

MER mercaptans

AMN amines

AMD amides

ET ethers

EP epoxides

ES esters

H hydrogen

CO carbon monoxide

SI silanes

UR ureas

OX oxalates

CN carbamates

CNA carbamic acids

CM carbonates

CMA carbonic acids

CA carboxylic acids

ANH anhydrides

KET ketones

OLE olefins

ACE acetylenes

HAL halides

SUL sulfonates

ALD aldehydes

NIT nitriles

HC hydrocarbons

CYP cyclopropanes

ABR alkylboranes

ADL aldols

AZ aziridines

SUO sulfoxides

Illustrative of asymmetric syntheses reactions encompassed within thescope of this invention include, for example, the followingreactant/product combinations:

    ______________________________________                                        REACTANT(S)         PRODUCT(S)                                                ______________________________________                                        OLE                 EP                                                        OLE, CO, H          ALD                                                       OLE, CO, H          CA                                                        ALD                 KET                                                       OLE, ALD            KET                                                       OLE, HC             HC                                                        OLE, CO             CA                                                        OLE, CO, AMN        AMD                                                       OLE                 AZ                                                        SUD                 SUO                                                       OLE, C0, AL         ES                                                        KET, H              AL                                                        EP, H               AL                                                        OLE, AMN            AMN                                                       OLE, AL             ET                                                        AL, CO              HC                                                        AL                  ALD                                                       OLE, HCN            NIT                                                       OLE, HS             SI                                                        OLE, CO, W          CA                                                        OLE                 OLE                                                       GR                  HC                                                        AH                  HAL                                                       OLE, H              HC                                                        OLE, BOR            AL                                                        OLE, BOR            ABR                                                       OLE, DZ             CYP                                                       KET, AL             AL                                                        ALD, ESE            ADL                                                       KET, ESE            ADL                                                       KET, HS             AL                                                        EP, CO, H           ALD                                                       EP, HCN             NIT                                                       ALD                 CA                                                        ______________________________________                                    

As indicated above, the processes of this invention can be conducted ina batch or continuous fashion, with recycle of unconsumed startingmaterials if required. The reaction can be conducted in a singlereaction zone or in a plurality of reaction zones, in series, or inparallel, or it may be conducted batchwise or continuously in anelongated tubular zone or series of such zones. The materials ofconstruction employed should be inert to the starting materials duringthe reaction and the fabrication of the equipment should be able towithstand the reaction temperatures and pressures. Means to introduceand/or adjust the quantity of starting materials or ingredientsintroduced batchwise or continuously into the reaction zone during thecourse of the reaction can be conveniently utilized in the processesespecially to maintain the desired molar ratio of the startingmaterials. The reaction steps may be effected by the incrementaladdition of one of the starting materials to the other. Also, thereaction steps can be combined by the joint addition of the startingmaterials to the optically active metal-ligand complex catalyst. Whencomplete conversion is not desired or not obtainable, the startingmaterials can be separated from the product and the recycled back intothe reaction zone.

The processes may be conducted in either glass lined, stainless steel orsimilar type reaction equipment. The reaction zone may be fined with oneor more internal and/or external heat exchanger(s) in order to controlundue temperature fluctuations, or to prevent any possible "runaway"reaction temperatures.

Finally, the optically active products of the process of this inventionhave a wide range of utility that is well known and documented in theprior art, e.g. they are especially useful as pharmaceuticals, flavors,fragrances, agricultural chemicals, and the like. Illustrativetherapeutic applications include, for example, non-steroidalanti-inflammatory drugs, ACE inhibitors, beta-blockers, analgesics,bronchodilators, spasmolytics, antihistamines, antibiotics, antitumoragents, and the like.

As used herein, the following terms have the indicated meanings:

    ______________________________________                                        Chiral     molecules which have one or more centers of                                   asymmetry.                                                         Achiral    molecules or processes which do not include                                   or involve at least one center of asymmetry.                       Prochiral  molecules which have the potential to be                                      converted to a chiral product in a particular                                 process.                                                           Chiral Center                                                                            any structural feature of a molecule that is a                                site of asymmetry.                                                 Racemic    a 50/50 mixture of two (2) enantiomers of                                     chiral compound.                                                   Stereoisomers                                                                            compounds which have identical chemical                                       construction, but differ as regards the                                       arrangement of the atoms or groups in space.                       Enantiomer stereoisomers which are non-superimposable                                    mirror images of one another.                                      Stereoselective                                                                          a process which produces a particular                                         stereoisomer in favor of others.                                   Enantiomeric                                                                             a measure of the relative amount of two (2)                        Excess (ee)                                                                              enantiomers present in a product.                                             Enantiomeric excess may be calculated by the                                  formula [amount of major enantiomer -                                         amount of minor enantiomer]/[amount of                                        major enantiomer + amount of minor                                            enantiomer].                                                       Optical Activity                                                                         an indirect measurement of the relative                                       amounts of stereoisomers present in a given                                   product. Chiral compounds have the ability to                                 rotate plane polarized light. When one                                        enantiomer is present in excess over                                          the other, the mixture is optically active.                        Optically Active                                                                         a mixture of stereoisomers which rotates plane                                polarized light due to an excess of one of the                                stereoisomers over the others.                                     Optically Pure                                                                           a single stereoisomer which rotates plane                                     polarized light                                                    Regioisomers                                                                             compounds which have the same molecular                                       formula but differing in the connectivity of                                  the atoms.                                                         Regioselective                                                                           a process which favors the production of a                                    particular regioisomer over all others.                            ______________________________________                                    

For purposes of this invention, the chemical elements are identified inaccordance with the Periodic Table of the Elements, CAS version,Handbook of Chemistry and Physics, 67th Ed., 1986-87, inside cover. Alsofor purposes of this invention, the term "hydrocarbon" is contemplatedto include all permissible compounds having at least one hydrogen andone carbon atom. In a broad aspect, the permissible hydrocarbons includeacyclic and cyclic, branched and unbranched, carbocyclic andheterocyclic, aromatic and nonaromatic organic compounds which can besubstituted or unsubstituted.

The following specific examples are supplied for the purpose of betterillustrating the invention. These examples are not intended, however, tolimit or restrict the scope of the invention in any way and should notbe construed as providing conditions, parameters, or values which mustbe utilized exclusively in order to practice the present invention.

EXAMPLES (General)

Gas chromatographic (GC) analyses were carded out on Hewlett Packard5890 instruments equipped with FID detectors. The enantiomeric excessesof the epoxides were determined by chiral GC. (Cyclodex B, ChiraldexG-PN) or HPLC (S,S-Whelk-0), or NMR in the presence of Eu(hfc)3. ¹ H and¹³ C NMR were recorded on Bruker NR200 or Bruker ARX400 spectrometer.Flash Column separations were accomplished using Merck silica gel(230-400 mesh) purchased from Aldrich. Mass spectra were recorded on aFinnigan SSQ 7000 mass spectrometer. The mass of the metal complexeswere determined using LCMS with an atmospheric pressure CI interphase.

EXAMPLE 1 Preparation of Ligand Precursor (1R,2R)-N-Picolinyl-1,2-Diphenylethylenediamine

A solution of (1R,2R)-1,2-diphenylethylenediamine (1.16 g, 4.74 mmol),picolinic acid (596 mg, 4.79 mmol, 1.01 eq.),N,N-dimethyl-4-aminopyridine (100 mg, 0.82 mmol, 0.17 eq.) and1,3-dicyclohexycarbodiimide (1.07 g, 5.2 mmol, 1.1 eq.) indichloromethane (40 ml) was stirred at room temperature under N₂ for 18hours. The reaction mixture was filtered and washed with water. Columnchromatography on silica gel using EtOAc/CH₂ Cl₂ (4:1) afforded 1.06 gof white solids as title compound (71% yield). NMR and GCMS confirmedthe structure.

EXAMPLE 2 Preparation of Ligand Picolinamide-Salicylidene

A mixture of the monoamide (from Example 1) and salicylaldehyde in equalmolar amounts in absolute ethanol (200 proof) was refluxed for threehours. TLC (EtOAc/CH₂ Cl₂, 3/2) showed the disappearance of themonoamide and appearance of a less polar component (higher Rf). Removalof the ethanol on rotovap gave the desired ligand in quantitative yield.The crude product was pure by NMR and was used in the next step withoutpurification.

EXAMPLE 3 Preparation of Mn-Amide-Salicylidene Catalyst

The ligand from Example 2 (0.92 mmol) and Mn(OAc)3 dihydrate (4.86 mmol,1.34 g, 5.2 eq.) were heated to reflux in 20 ml of 190 proof ethanol for18 hours. TLC analysis (25% acetone in hexanes) showed almost completedisappearance of the ligand. After allowing the reaction to cool to 40°C., LiCl (4.66 mmol, 2 g, 5 eq.) was added and reflux was resumed for2.5 hours. Ethanol was removed by rotovap and the residue was taken inCH₂ Cl₂, and washed 2-3 times with half-saturated aqueous NaCl solution.The complex was isolated in 43% yield by column on silica gel using amixture of 35% acetone in hexanes as eluent. Mass analysis showedmolecular ion as follows: ##STR11##

EXAMPLES 4-41 Epoxidation of Olefins

The following procedure was used to epoxidize the various olefins shownin Tables 1-8 by the catalysts indicated and which were prepared inExamples 1-3. The manganese complex (5-20 mg, 1-5 mol percent versus theolefin) was dissolved in 1-2 ml CH₂ Cl₂ at room temperature. The olefin(˜30 to 120 mg, 0.2 to 1.0 mmol) was added and the mixture was cooled to0° C. In some cases, a known mount of decane was added as internalstandard for GC analysis. Cold buffered bleach (0° C., pH=11, made fromClorox, 2 mL) was added at 0° C. and the reaction mixture was stirred atroom temperature for 6-40 hours. The progress of the reaction wasmonitored by GC analysis. Hexane (2 mL) was added and the organic layerwas separated and ee of the epoxide was analyzed by GC, LC, or NMR.

                  TABLE 1                                                         ______________________________________                                        Epoxidation of Olefins with Complex                                            ##STR12##                                                                                                  Epoxides                                                                              Epoxides                                Example              Cat.     Ratio   ee (%)                                  Number Substrate     mol %    (cis/trans)                                                                           cis/trans                               ______________________________________                                        4 5                                                                                   ##STR13##    5.2 1.1  58/42 65/35                                                                           34/3 39/8                               6 7                                                                                   ##STR14##    4.6 0.89 0/100 0/100                                                                           0/27 0/20                                       ##STR15##    4.5              39                                      9 10                                                                                  ##STR16##    4.7 0.97         34 22                                   ______________________________________                                    

                  TABLE 2                                                         ______________________________________                                        Epoxidation of Olefins by Bleach with Complex                                  ##STR17##                                                                    Exam-                  Cat.                                                   ple                           Epoxides                                                                              Epoxides                                Num-                   mol    Ratio   ee (%)                                  ber   Substrate        %      (cis/trans)                                                                           cis/trans                               ______________________________________                                        11                                                                                   ##STR18##       3.8    78/22   56/14                                   12                                                                                   ##STR19##       4.7    0/100   0/31                                    13                                                                                   ##STR20##       3.1            46                                      14                                                                                   ##STR21##       3.5            36                                      15                                                                                   ##STR22##       4.9            15                                      ______________________________________                                    

                                      TABLE 3                                     __________________________________________________________________________    Epoxidation of Olefins with Complex                                            ##STR23##                                                                    Example           Cat.  Epoxides Epoxides                                     Number                                                                             Substrate    mol % Ratio (cis/trans)                                                                      ee (%) cis/trans                             __________________________________________________________________________    16 17                                                                               ##STR24##   3.3 (0° C.) 3.1 (r.t)                                                        88/12 70/30                                                                            62/10 58/6                                   18                                                                                  ##STR25##   4.0   0/100    0/40                                         19                                                                                  ##STR26##   2.8            50                                           20                                                                                  ##STR27##   4.1            13                                           21                                                                                  ##STR28##   4.5            7                                             22 23                                                                              ##STR29##   4.7 4.7        34 (with PPyO) 28                            __________________________________________________________________________

                  TABLE 4                                                         ______________________________________                                        Epoxidation of Olefins with Complex                                            ##STR30##                                                                                                  Epoxides                                                                              Epoxides                                Example              Cat.     Ratio   ee (%)                                  Number Substrate     mol %    (cis/trans)                                                                           cis/trans                               ______________________________________                                        24                                                                                    ##STR31##    4.5      76/24   55/6                                    25                                                                                    ##STR32##    5.3      0/100   0/39                                    26                                                                                    ##STR33##    5.6              50                                      27                                                                                    ##STR34##    3.3              26                                      ______________________________________                                    

                  TABLE 5                                                         ______________________________________                                        Epoxidation of Olefins with Complex                                            ##STR35##                                                                                                  Epoxides                                                                              Epoxides                                Example              Cat.     Ratio   ee (%)                                  Number Substrate     mol %    (cis/trans)                                                                           cis/trans                               ______________________________________                                        28                                                                                    ##STR36##    5        84/16   37/21                                   29                                                                                    ##STR37##    5        0/100   0/27                                    30                                                                                    ##STR38##    5                38                                      31                                                                                    ##STR39##    5                25                                      ______________________________________                                    

                  TABLE 6                                                         ______________________________________                                        Epoxidation of Olefins by Bleach with Complex                                  ##STR40##                                                                                                  Epoxides                                                                              Epoxides                                Example              Cat.     Ratio   ee (%)                                  Number Substrate     mol %    (cis/trans)                                                                           cis/trans                               ______________________________________                                        32                                                                                    ##STR41##    5.7      70/30   36/15                                   33                                                                                    ##STR42##    4.4      0/100   0/33                                    34                                                                                    ##STR43##    4.5              41                                      35                                                                                    ##STR44##    3.6              13                                      ______________________________________                                    

                  TABLE 7                                                         ______________________________________                                        Epoxidation of Olefins with Complex                                            ##STR45##                                                                                                  Epoxides                                                                              Epoxides                                Example              Cat.     Ratio   ee (%)                                  Number Substrate     mol %    (cis/trans)                                                                           cis/trans                               ______________________________________                                        36                                                                                    ##STR46##    4.8      32/68   14/3                                    37                                                                                    ##STR47##    5.1              27                                      ______________________________________                                    

                  TABLE 8                                                         ______________________________________                                        Epoxidation of Olefins by Bleach with Complex                                  ##STR48##                                                                                                  Epoxides                                                                              Epoxides                                Example              Cat.     Ratio   ee (%)                                  Number Substrate     mol %    (cis/trans)                                                                           cis/trans                               ______________________________________                                        38                                                                                    ##STR49##    4.1      67/33   9/30                                    39                                                                                    ##STR50##    5.5      0/100   0/35                                    40                                                                                    ##STR51##    4.7              26                                      41                                                                                    ##STR52##    1.5              7                                       ______________________________________                                    

As previously mentioned, the novel catalysts have a wide range ofapplications and set forth below are examples of such utility.

EXAMPLE 42 Asymmetric Hydrosilylation of Acetophenone

The catalyst (0.020 g) of Example 3 is charged to a 50 ml Schlenk flaskunder nitrogen. Tetrahydrofuran (THF) (5.0 ml) is added to dissolve thecatalyst. 0.58 ml of acetophenone and 0.93 ml of diphenylsilane areadded to the flask via syringe. The solution is stirred under nitrogenfor 18 hours. The solution is treated with 10 ml of 10% hydrochloricacid and is extracted two times with 10 ml of diethyl ether. Thissolution is analyzed by GC on a Chiraldex B-PH column which can separatethe two enantiomers of the resulting sec-phenethyl alcohol. Thisanalysis indicates an 80:20 ratio of the R and S enantiomers for an eeof 60%.

EXAMPLE 43 Asymmetric Hydrocyanation of Styrene

The catalyst (0.15 g) of Example 3 is charged to a 50 ml Schlenk flaskunder nitrogen. Deoxygenated THF (10 ml) is added, and the solution isstirred for 30 minutes. 2.0 ml of styrene and 2.00 ml of acetonecyanohydrin are added to the flask via syringe. The solution is stirredfor 24 hours at 25° C.

A portion of this solution is analyzed by GC to determine productcomposition. An isomer ratio of 2:1 (α-methylbenzylcyanide:hydrocinnamonitrile) is observed. A second portion of thissolution is analyzed by GC on a Chiraldex G-TA column which can separatethe two enantiomers of the resulting α-methylbenzyl cyanide. Thisanalysis indicates an 82:18 ratio of the enantiomers for an ee of 64%.

EXAMPLE 44 Asymmetric Transfer Hydrogenation of Acetophenone

The catalyst (0.020 g) of Example 3 is charged to a 50 ml Schlenk flaskunder nitrogen. THF (5.0 ml) is added to dissolve the catalyst. To thissolution is added 5.0 ml of 2-propanol, 0.58 ml of acetophenone, and0.012 g of potassium hydroxide. The solution is stirred under nitrogenfor 24 hours. This reaction mixture is analyzed by GC on a ChiraldexB-PH column which can separate the two enantiomers of the resultingsec-phenylethyl alcohol. This analysis indicates a 60:40 ratio of the Sand R enantiomers for an ee of 20%.

EXAMPLE 45 Asymmetric Hydroboration of Styrene

The catalyst (0.050 g) of Example 3, excluding acetone, is charged to a50 ml Schlenk flask under nitrogen. Distilled 1,2-dimethoxyethane (2.0ml) is added to the flask. 0.23 ml of styrene and 0.23 ml ofcatecholborane are added to the flask via syringe. The solution isstirred under nitrogen for two hours. The solution is treated with 4 mlof methanol, 4.8 ml of 3.0 mol/liter sodium hydroxide solution, and 0.52ml of 30% hydrogen peroxide. The solution is stirred for three hours andis extracted with 10 ml of diethyl ether. A portion of this solution isanalyzed by GC to determine product composition. An isomer ratio of 3:1(sec-phenethyl alcohol:2-phenylethanol) is observed. A second portion ofthis solution is analyzed by GC on a Chiraldex B-PH column which canseparate the two enantiomers of the resulting sec-phenethyl alcohol.This analysis indicates a 61:39 ratio of the S and R enantiomers for anee of 22%.

EXAMPLE 46 Asymmetric Cyclopropanation of Styrene

The catalyst (0.085 g) of Example 3 is charged to a 25 ml Schlenk flaskunder nitrogen. Toluene (5.0 ml) is added to the flask under nitrogen.0.10 ml of triethylamine is added to the flask via syringe, and thesolution is stirred under nitrogen liar 15 minutes. 5.0 ml of styrene isadded by syringe followed by 0.250 ml of ethyldiazoacetate. The solutionis stirred under nitrogen for two hours. A portion of the reactionmixture is analyzed by GC to determine product composition. An isomerratio of 2.1:1 (trans:cis) is observed for the product cyclopropanes. Asecond portion of this solution is analyzed by GC on a Chiraldex B-PHcolumn which can separate the two enantiomers of the resultingcis-ethyl-2-phenylcyclopropanecarboxylate. This analysis indicates a63:37 ratio of the cis cyclopropane enantiomers for an ee of 26%.

EXAMPLE 47 Asymmetric Aldol Condensation of Benzaldehyde & MethylTrimethylsilyl Dimethylketene Acetal

The catalyst (0.050 g) of Example 3 is charged to a 50 ml Schlenk flaskunder nitrogen. Dichloromethane (2.0 ml) is added to the flask undernitrogen. 0.20 ml of benzaldehyde and 0.40 ml of methyl trimethylsilyldimethylketene acetal is added to the flask via syringe. The solution isstirred under nitrogen for 18 hours. The solution is treated with 10 mlof 10% hydrochloric acid and is extracted two times with 10 ml ofdiethyl ether. This solution is analyzed by GC on a Chiraldex B-PHcolumn which can separate the two enantiomers of the resultingmethyl-2,2-dimethyl-3-phenyl-3-trimethylsiloxypropionate. This analysisindicates a 75:25 ratio of the enantiomers for an ee of 76%.

Although the invention has been illustrated by certain of the precedingexamples, it is not to be construed as being limited thereby; butrather, the invention encompasses the generic area as hereinbeforedisclosed. Various modifications and embodiments can be made withoutdeparting from the spirit and scope thereof.

What is claimed is:
 1. A composition of matter having the formula:##STR53## wherein R₁ and R₂ are independently selected from the groupconsisting of hydrogen, substituted or unsubstituted alkyl C₁ -C₅₀ ;substituted and unsubstituted phenyl, naphthyl, and anthracyl, and acyclic ring encompassing both R₁ and R₂ and containing a total of 3 to50 atoms selected from the group consisting of carbon atoms, oxygenatoms, nitrogen atoms, sulfur atoms, and mixtures thereof, with theproviso that the substituents on the alkyl, phenyl, naphthyl, anthracyl,and cyclic rings can be nitro, halogen, alkoxy, carboxylate, amino,amide, silyl, and siloxyl; R₃ -R₁₁ are independently selected from thegroup consisting of substituted or unsubstituted alkyl and aryl; nitro;halogen; hydrogen; alkoxy; carboxylate; amino; amide; silyl; andsiloxyl; R₄ and R₅, R₅ and R₆, and R₆ and R₇ may also (in addition tothe above) form a cyclic ring containing a total of 2 to 6 atomsselected from the group consisting of carbon atoms, oxygen atoms,nitrogen atoms, sulfur atoms, and mixtures thereof and said ring can besubstituted or unsubstituted; R₉ and R₁₀ are independently selected fromthe group consisting of hydrogen; alkyl C₁ -C₂₀ ; substituted andunsubstituted phenyl, naphthyl, and anthracyl; and a cyclic ringencompassing both R₉ and R₁₀ and containing a total of 2 to 6 atomsselected from the group consisting of carbon atoms, oxygen atoms,nitrogen atoms, sulfur atoms, and mixtures thereof; M is a transitionmetal ion; A is an anion; n is either 0, 1, or 2; and (C₁), (C_(n)), and(C₂) are independently or jointly part of an unsubstituted orsubstituted aryl group.
 2. The composition as set forth in claim 1wherein M is selected from the group consisting of manganese, cobalt,nickel, iron, rhenium, ruthenium, rhodium, chromium, technetium,palladium, platinum, osmium, copper, tellurium, titanium, vanadium,molybdenum, and gadolinium.
 3. The composition as set forth in claim 1wherein M is manganese.
 4. The composition as set forth in claim 1wherein A is selected from the group consisting of halide, acetate,sulfonate, triflate, tosylate, carboxylate, PF₆, BF₄, B(R)₄, and Rwherein R is either alkyl or substituted or unsubstituted aryl.
 5. Thecomposition as set forth in claim 1 wherein A is chlorine.
 6. Thecomposition as set forth in claim 1 wherein R₉ and R₁₀ collectively formpart of a cyclic ring which is phenyl.
 7. The composition as set forthin claim 1 wherein R₉ and R₁₀ are both phenyl groups.
 8. The compositionas set forth in claim 1 wherein said catalyst is non-chiral.
 9. Thecomposition as set forth in claim 1 wherein said catalyst is chiral. 10.The composition as set forth in claim 1 wherein either one or both of C₁and C₂ are a chiral carbon center.
 11. The composition as set forth inclaim 4 wherein the halide is selected from the group consisting ofchlorine, bromine, fluorine, and iodine.
 12. The composition as setforth in claim 1 wherein (C_(n)) is 0; M is manganese; R₅ is n-butyl; R₈and R₁₁ are hydrogen; R₉ and R₁₀ are both phenyl; R₃ is1,1-diethylpropyl; and R₂, R₆, and R₇ are hydrogen.
 13. A composition ofmatter having the formula: ##STR54## wherein n is either 0, 1, or 2; Mis a transition metal ion; A is an anion; R₁ -R₉ are independentlyselected from the group consisting of substituted and unsubstitutedalkyl and aryl; nitro; halogen; alkoxy; carboxylate; amino; amide;silyl; and siloxyl; R₁₀ and R₁₁ are independently selected from thegroup consisting of hydrogen; alkyl C₁ -C₂₀ ; substituted andunsubstituted phenyl, naphthyl, anthracyl; and a cyclic ringencompassing both R₁₀ and R₁₁ and containing a total of two to six atomsselected from the group consisting of carbon atoms, oxygen atoms,nitrogen atoms, sulfur atoms, and mixtures thereof; R₁₂ and R₁₃ areindependently selected from the group consisting of hydrogen; alkyl C₁-C₂₀ ; phenyl, naphthyl, and anthracyl; (C₁), (C_(n)), and (C₂) areindependently or jointly part of an unsubstituted or unsubstituted arylgroup; and R₁ and R₂, R₂ and R₃, R₃ and R₄, R₅ and R₆, R₆ and R₇, and R₇and R₈ may form a cyclic ring containing a total of two to six atomsselected from the group consisting of carbon atoms, oxygen atoms,nitrogen atoms, sulfur atoms, and mixtures thereof, and said ring can besubstituted or unsubstituted.
 14. The composition as set forth in claim13 wherein M is selected from the group consisting of manganese, cobalt,nickel, iron, rhenium, ruthenium, rhodium, technetium, palladium,platinum, osmium, copper, tellurium, titanium, vanadium, molybdenum, andgadolinium.
 15. The composition as set forth in claim 13 wherein M ismanganese.
 16. The composition as set forth in claim 13 wherein A isselected from the group consisting of halide, acetate, triflate,tosylate, carboxylate, PF₆, BF₄, B(R)₄, and R₄ wherein R is either alkylor substituted or unsubstituted aryl.
 17. The composition as set forthin claim 13 wherein A is chlorine.
 18. The composition as set forth inclaim 13 wherein R₁₀ and R₁₁ collectively form part of a cyclic ringwhich is phenyl.
 19. The composition as set forth in claim 13 whereinR₁₀ and R₁₁ are both phenyl.
 20. The composition as set forth in claim13 wherein said catalyst is non-chiral.
 21. The composition as set forthin claim 13 wherein said catalyst is chiral.
 22. The composition as setforth in claim 13 wherein either one or both of C₁ and C₂ are a chiralcarbon center.
 23. The composition as set forth in claim 16 wherein thehalide is selected from the group consisting of chlorine, bromine,fluorine, and iodine.
 24. The composition as set forth in claim 13wherein n is 0; M is manganese; R₃ and R₇ are n-butyl; R₁₂ and R₁₃ arehydrogen; R₁₀ and R₁₁ are both phenyl; R₅ is 1,1-diethylpropyl; and R₁,R₂, R₃, R₄, R₆, R₈, and R₉ are hydrogen.
 25. A composition of matterhaving the formula: ##STR55##
 26. A composition of matter having theformula: ##STR56## wherein M is a transition metal ion; A is an anion;and R₁ -R₂₁ are independently selected from the group consisting ofsubstituted and unsubstituted alkyl and aryl; nitro; hydrogen; halogen;alkoxy; carboxylate; amino; amide; silyl; and siloxyl.
 27. A compositionof matter having the formula: ##STR57##
 28. A composition of matterhaving the formula: ##STR58##
 29. A composition of matter having theformula: ##STR59##
 30. A composition of matter having the formula:##STR60##
 31. A composition of matter having the formula: ##STR61## 32.A composition of matter having the formula: ##STR62##
 33. A compositionof matter having the formula: ##STR63##
 34. The composition as set forthin claim 1 wherein A is not present.
 35. A composition of matter havingthe formula ##STR64## wherein M is a metal having an oxidation state of2, and R₁ -R₁₁ have the same meaning as set forth in claim
 1. 36. Thecomposition of matter of claim 35 wherein M is a metal having anoxidation state of 1 or 0 and there is also present a cation.
 37. Acomposition of matter having the formula: ##STR65## where R is t-butylor triphenylmethyl.
 38. A composition of matter having the formula:##STR66## where R is t-butyl or triphenylmethyl.
 39. A composition ofmatter having the formula: ##STR67## where R is t-butyl ortriphenylmethyl.